It is of great advantage to both the patient and clinician that medication be formulated so that it may be administered in a minimum number of daily doses from which the drug is uniformly released over a desired extended period of time. Until now, this has been accomplished in several different ways. Medicinal agents are either coated with varying thicknesses of a relatively insoluble material or are embedded into a rigid lattice of resinous material. The medicinal agent is continuously made available for absorption into the blood stream to replace the amount eliminated while the dosage form is passing through the gastro-intestinal tract of the patient. However, certain types of medicinal agents are not suited to absorption during passage through the gastro-intestinal tract. For example, most acidic medicinals are principally absorbed from the stomach, whereas most basic medicinals are absorbed primarily from the intestines.
U.S. Pat. No. 3,458,622 to Hill discloses a controlled release tablet for the administration of medicinal agents over a prolonged period of up to about eight hours. This patent discloses a compressed tablet for the prolonged release of a medicament containing that medicament in a core formed from a polymeric vinyl pyrrolidone, preferably polyvinyl pyrrolidone (PVP), and a carboxyvinyl hydrophilic polymer (hydrocolloid) such as those marketed under the trademark Carbopol wherein the combined weight of the two polymeric materials may exceed half the weight of medicament but should be kept below about 75% of the weight of medicament. The tablet is formed employing a wet granulation technique. The core material formed from the two polymeric substances provides the controlled release effect by forming a complex of lower water-solubility under the action of water or gastric fluid, without swelling of the polymeric substances. This complex is gum-like in consistency and retards the diffusion of active ingredient from the tablet. The controlled release rate of the drug is dependent upon the interaction of the two principal ingredients, the polymer and the hydrocolloid, in the presence of water to form a gummy complex of low solubility. Since little of the gummy complex is present initially, the drug at or near the surface dissolves fairly rapidly and there is an initial surge wherein a relatively large amount of drug is released in the beginning for a period of about one hour. As the colloid complex is formed, once aqueous solution penetrates the surface of the tablet, the gel retards the dissolution of the drug out of the tablet.
DE No. 3314003-A dated Apr. 4, 1983 (Boehringer Ingelheim) is similar in disclosure U.S. Pat. No. 3,458,622 to Hill and discloses divisible, delayed release tablets containing a molecular dispersion of active ingredient in a polyacrylate carrier together with lactose, polyvinylpyrrolidone, starch, colloidal silicic acid and magnesium stearate, which are prepared by wet granulation.
U.S. Pat. No. 4,252,786 to Weiss et al recognizes the initial surge problem in the Hill patent and resolves same by applying a rupturable relatively water-insoluble water-permeable film formed of a combination of hydrophobic and hydrophilic polymers over an insoluble swelling type delayed release matrix or core containing the medicament which core includes a blend of polyvinyl pyrrolidone and a carboxyvinyl hydrophilic polymer. Weiss et al in Column 2 states as follows:
"Initially, while the film is intact, the release of the drug contained in the matrix is primarily controlled by diffusion of solvent and solute molecules through the film. As water or gastric fluid permeates through the film, the gummy complex forms and the slight swelling of the complex causes the film to rupture or erode. The release rate is then controlled by the gummy complex. The application of a relatively water insoluble, water permeable film primarily controls the drug release rate while the matrix gel is being generated and a smoother, gradual, more uniform release rate is achieved during the entire period of about eight to twelve hours, approaching a zero order release pattern. The release pattern of the core, upon application of the film, can be varied over a range by varying the composition and amount of film-forming mixture."
U.S. Pat. No. 4,140,755 to Sheth et al discloses a sustained release formulation in the form of sustained release tablets which are hydrodynamically balanced to have a bulk density (specific gravity) of less than 1 in contact with gastric fluid and which will therefore remain floating in gastric fluid which has a specific gravity of between 1.004 and 1.010. The Sheth et al sustained release formulation contains a homogeneous mixture of one or more medicaments with one or more hydrophilic hydrocolloids, such as hydroxypropyl methyl cellulose having a viscosity of 4000 cps. The hydrocolloids when contacted with gastric fluid at body temperatures form a sustained gelatinous mix on the surface of the tablet causing the tablet to enlarge and acquire a bulk density of less than 1. The medicament is slowly released from the surface of the gelatinous mix which remains buoyant in the gastric fluid.
All of the medicament in the tablet disclosed in the Sheth et al patent is released in the stomach.
U.S. Pat. Nos. 4,309,404 and 4,248,857 to DeNeale et al disclose slow release formulations for many different drugs and classes of drugs including propranolol and other antihypertensives which formulations are formed of a core material containing the active drug (31-53%), carboxypolymethylene (7-14.5%), zinc oxide (0-3%), stearic acid (4.5 to 10%) and mannitol (3 to 30%); a seal coating surrounding the core; and a sugar coating surrounding the seal coating.
U.S. Pat. No. 4,309,405 to Guley et al discloses a sustained release tablet similar to that disclosed in DeNeale et al (U.S. Pat. No. 4,309,404) except that the core contains 20 to 70% drug, 30 to 72% of a mixture of a water-soluble polymer such as hydroxypropylmethyl cellulose or hydroxypropyl cellulose and water-insoluble polymer (ethylcellulose alone or in admixture with carboxypolymethylene, hydroxypropyl cellulose and the like).
Each of the DeNeale et al and Guley et al patents disclose that their compositions provide substantially zero order release of the core contained drug for about 12 hours following the first hour of administration. Thus, zero order release is only obtained after the initial surge of release of drug in the first hour.
U.S. Pat. No. 4,259,314 to Lowey discloses a controlled long-acting dry pharmaceutical composition which includes a dry carrier formed from a mixture of hydroxypropylmethyl cellulose (viscosity of 50 to 4000 cp in 2% aqueous solution at 20.degree. C.) and hydroxypropyl cellulose (viscosity of 4000 to 6500 cp for a 2% aqueous solution at 25.degree. C.) which dry carrier is employed with a therapeutic agent among which include aspirin, ascorbic acid and nitroglycerin.
U.S. Pat. Nos. 3,065,143 to Christenson et al, 3,147,137 to Playfair, 3,444,290 to Wal et al, 3,427,378 to Henderson et al, 3,555,151 to Kaplan et al, 3,574,820 to Johnson et al, and 3,976,764 to Watanabe and 4,173,626 to Dempski et al disclose various sustained release tablets which include gelling agents none of which includes as the active ingredient an angiotensin converting enzyme inhibitor.
U.S. Pat. No. 4,389,393 to Schor et al discloses a carrier base material to be combined with a therapeutically active medicament into a solid dosage form. The carrier base material is one or more hydroxypropylmethyl celluloses, or a mixture of one or more hydroxypropylmethyl celluloses and up to 30% by weight of the mixture of methyl cellulose, sodium carboxymethyl cellulose and/or other cellulose ether, wherein at least one of the hydroxypropylmethyl celluloses has an average molecular weight of at least 50,000, the carrier base material constituting less than one-third of the weight of the solid unit dosage form.
U.S. Pat. No. 4,434,153 to Urquhart discloses a drug delivery system formed of a swellable hydrogel reservoir or matrix such as an acrylic acid polymer matrix containing tiny pills formed of a wall surrounding a drug core.